Gynaecological disorders and diseases considerably reduce the quality of life of women and frequently result, in some cases in addition to unbearable pain, in infertility. One of the most common diseases in women of child-bearing age (5% to 10%) is endometriosis. Associated with it are severe pain during menstruation and a limited fertility rate to sterility. In the case of the myoma, a benign tumour in the muscle tissue of the uterus, the incidence is high too (in 10 to 25% of women in their 30s). Myomas may cause heavy abnormal menstrual bleeding (hypermenorrhoea), painful menstruation (dysmenorrhoea) and/or intermenstrual bleeding (metrorrhagia, menorrhagia) and each, depending on the condition, may also result in limited fertility. In addition to dysmenorrhoea caused by endometriosis and by myomas, dysmenorrhoea that is caused by functional disorders (by hormonal and vegetative disorders) also occurs.
The gonal steroids (oestrogens, gestagens), which are under the control of the hypothalamic-pituitary system, and growth factors (including also cytokines) play a decisive role in the clinical syndromes described. Treatment of such diseases and disorders is usually effected with hormones, such as LHRH analogues (Lemay, A. et al., Fertil. Steril., 41, 863-871 (1984)). In some women, however, these are not tolerated without side effects. For example, it is known that treatment with LHRH agonists may result in side effects such as, for example, hypo-oestrogenaemia (risk of osteoporosis) (Dawood, M. Y. et al., Fertil. Steril. 52, 21-25, (1989)) and treatment with danazol may result in androgenisation phenomena (Dmowski, W. P. et al., Am. J. Obstet. Gynecol., 130, 41-48 (1978)).
No established and proven long-term medicament treatment has existed hitherto for myomas. The medicament treatment currently used is associated with distinct side effects. For example, the use of LHRH agonists for more than six months results in a hypo-oestrogenic state in women (Matta, W. H. et al., Br. Med. J., 294, 1523-1525, (1987)) and, associated with that, a reduction in bone density, which increases the risk of osteoporosis (Dawood, M. Y. Int. J. Gynecol. Obstet., 40, 29-42 (1993)). Other side effects associated with oestrogen withdrawal (hot flashes) are also described by Dawood.
Studies for the treatment of gynaecological disorders with LHRH analogues and oestrogens—so-called Add-Back or HRT treatment regimes—are known for the purpose of avoiding those side effects. The discovery of an oestrogen dose that completely prevents a reduction in bone density using LHRH agonist therapy (Howell, R. et al., Fertil, Steril. 64, 474-481, (1995)) without at the same time stimulating endometriosis or stimulating the endometrium, which may result in endometrium hyperplasia and, associated with that, endometrium carcinomas, has hitherto been unsuccessful, however.